As a noninvasive method for measuring concentration and distribution of chemicals in the living brain MRS is an important tool for studying brain function and disorders. However, robust measurement of MRS signals requires highly sophisticated design, implementation and maintenance of various MRS techniques. MRS technology has been a very active research area, attracting major effort from top magnetic resonance research centers around the world. Clinical magnetic resonance imaging scanners optimized for performing structural and functional imaging studies also present daunting obstacles for MRS technical development. Most of the MRS protocols at NIH were developed and implemented by the MRS core. 1) Automatic correction of magnetic field inhomogeneity. It is essential to optimize the homogeneity of magnetic field for all MRS experiments because field inhomogeneity can easily destroy the critical separation of different chemicals. More importantly, an inhomogeneous field makes effective suppression of tissue water signal difficult, therefore making reliable detection of more dilute chemicals impossible. This is particularly the case for anatomical regions of interest to psychiatric research. We have refined and implemented an automatic shimming method called FASTMAP which is optimal for localized MRS studies. This method consistently out performs the automatic shimming method provided by the manufacturer. It has already greatly improved the quality of proton glutamate editing and 13C MRS experiments. Implementation of this method on the new Siemens 7 Tesla scanner was completed during 2011-2012. 2) N-acetylaspartate mapping. The MRS core maintains a chemical shift imaging techique for mapping distribution of the neuronal marker N-acetylaspartate on 1.5 and 3 Tesla General Electric scanners. This method simultaneously generates images of N-acetylaspartate, creatine, and choline-containing compounds. Patient movements can cause artifacts in N-acetylaspartate imaging. The patient movements can be compensated for by using the signal of the partially suppressed water. Unsuppressed water would be too strong to be separated from the metabolite signals, so the N-acetylaspartate mapping sequence was revised to use residual unsuppressed water as a navigator to track and correct for patient motion. 3) Glutathione detection. Glutathione is a marker for oxidative stress. Many psychiatric and neurological disoders (such as schizophrenia, Alzheimer's disease and stroke) are associated with abnormal glutathione concentration. In collaboration with Steven Warach (NINDS) a glutathione editing method was developed on the Philip 3 Tesla scanner at Suburban Hospital for studying stroke patients. This method uses a selective editing pulse placed on the cysteinyl alpha proton of glutathione to remove the overlapping signals from creatine and GABA. Dr. Warach's group has used this method to study stroke patients. 4) Carbon-13 MRS. By using carbon-13 labeled glucose or the glial-specific substrate acetate, brain energetics and glutamate and glutamine cycling flux can be measured. Previously we invented a method for carbon-13 MRS by combining low power stochastic decoupling and intravenous infusion of glucose with a carbon-13 label at the C2 position. This strategy makes it possible to perform viable carbon-13 MRS within the hardware constraints at the NIH. Using this strategy, we recently acquired high quality carbon-13 MRS data from both the occipital and frontal lobes of healthy subjects and showed that it is possible to simultaneously detect two labeling pathways. We are currently attempting to develop this method on the new 7 Tesla Siemens scanner. 5) Proton glutamate editing. Previously we implmented a single-voxel glutamate editing methodwith correction of eddy current effects for measuring glutamate concentration at 3 Tesla. The method requires several dozen echo time averages, therefore making it incompatible with the robust conventional chemical shift imaging. We are developing a new glutamate editing method which needs a single echo time to isolate the glutamate H4 signal at both 3 and 7 Tesla field strengths. Novel spectral fitting method that improves the reliability of glutamate quantification was also developed during 2011-2012. 6) GABA editing. Previously we implemented and refined a method for measuring GABA. Similar to N-acetylaspartate imaging, patient movements can lead to difficulty in accurate determination of GABA. A navigator strategy based on residual water was used to track and correct for patient movement. Special data processing software was also written to correct for phase changes because of patient motion. The improvements of the corrections have been quantified and applied to studies of human subjects during 2011-2012. 7) NAAG editing. We have successfully developed a MRS method for measuring the dipeptide neurotransmitter N-acetylaspartylglutamate (NAAG) which plays an important role in glutamate signaling. Our current method uses regularized lineshape deconvolution based on the L-curve method combined with echo time averaging to separate NAAG from NAA. A further improvement in data quality was made using soft constraints during 2011-2012.